Amplitude spectrum distance: measuring the global shape divergence of protein fragments

International audienceBackground: In structural bioinformatics, there is an increasing interest in identifying and understanding the evolution of local protein structures regarded as key structural or functional protein building blocks. A central need is then to compare these, possibly short, fragments by measuring efficiently and accurately their (dis)similarity. Progress towards this goal has given rise to scores enabling to assess the strong similarity of fragments. Yet, there is still a lack of more progressive scores, with meaningful intermediate values, for the comparison, retrieval or clustering of distantly related fragments. Results: We introduce here the Amplitude Spectrum Distance (ASD), a novel way of comparing protein fragments based on the discrete Fourier transform of their C α distance matrix. Defined as the distance between their amplitude spectra, ASD can be computed efficiently and provides a parameter-free measure of the global shape dissimilarity of two fragments. ASD inherits from nice theoretical properties, making it tolerant to shifts, insertions, deletions, circular permutations or sequence reversals while satisfying the triangle inequality. The practical interest of ASD with respect to RMSD, RMSDd , BC and TM scores is illustrated through zinc finger retrieval experiments and concrete structure examples. The benefits of ASD are also illustrated by two additional clustering experiments: domain linkers fragments and complementarity-determining regions of antibodies.Conclusions: Taking advantage of the Fourier transform to compare fragments at a global shape level, ASD is an objective and progressive measure taking into account the whole fragments. Its practical computation time and its properties make ASD particularly relevant for applications requiring meaningful measures on distantly related protein fragments, such as similar fragments retrieval asking for high recalls as shown in the experiments, or for any application taking also advantage of triangle inequality, such as fragments clustering. ASD program and source code are freely available at: http://www.irisa.fr/dyliss/public/ASD/

Herbicide effects on freshwater benthic diatoms: Induction of nucleus alterations and silica cell wall abnormalities

Benthic diatoms are well known bio-indicators of river pollution by nutrients (nitrogen and phosphorus). Biological indexes, based on diatom sensitivity for non-toxic pollution, have been developed to assess the water quality.Nevertheless, they are not reliable tools to detect pollution by pesticides. Many authors have suggested that toxic agents, like pesticides, induce abnormalities of the diatom cell wall (frustule). High abnormal frustule abundances have been reported in natural diatom communities sampled in streams contaminated by pesticides. However, no direct link was found between the abundances of abnormal frustules in these communities and the pesticide concentrations in stream water. In the present study, a freshwater benthic diatomcommunity, isolated fromnatural biofilm and cultured under controlled conditions, was treated with a known genotoxic herbicide, maleic hydrazide (MH). Cells were exposed to three concentrations of MH (5×10−6, 10−6, 10−7 M) for 6 h followed by a 24 h-recovery time. After MH treatments, nucleus alterations were observed: abnormal nucleus location, micronucleus, multinuclear cell or disruption of the nuclear membrane. A dose-dependent increase of nuclear alterations was observed. The difference between the control (9.65 nuclear alterations per 1000 cells observed (9.65‰), S.D. = 4.23) and the highest concentrations (29.40‰, S.D. = 8.49 for 10−6Mand 35.96‰, S.D. = 3.71 for 5×10−6 M)was statistically significant (Tukey test, P < 0.05). Diatoms also exhibited frustules with deformed morphology and abnormal ornamentation. Significantly increased abundances of abnormal frustules were observed for the highest concentrations (10−6 and 5×10−6 M; Tukey test, P < 0.05). These two parameters tended to increase together (Pearson correlation = 0.702, P < 0.05). The results suggest that the induction of abnormal frustules could be associated with the genotoxic effects of MH. The alterations observed could be related to the effects of MH on the synthesis of the proteins involved in frustule formation or in the regulation of the cytoskeleton of the diatom cells

Sensitivity of freshwater periphytic diatoms to agricultural herbicides

The biomonitoring of pesticide pollution in streams and rivers using algae such as diatoms remains difficult. The responses of diatomcommunities to toxic stress in streamwater are disturbed by the variations of environmental parameters. In this study, periphytic algae collected in situwere exposed under controlled conditions to two major herbicides used in French agriculture (isoproturon and s-metolachlor). Three exposure regimes were tested: 5 and 30gL−1 for 6 days and 30gL−1 for 3 days followed by a recovery period of 3 days. The algal biomasses were assessed from pigment concentrations (chlorophyll a and c) and from live cell density. The highest concentration (30gL−1) of isoproturon inhibited the biomass increase statistically significantly. In periphyton exposed to 5 and 30gL−1 of s-metolachlor, chlorophyll c concentration and live cell densitywere also statistically significantly lower than in the control. Periphyton left to recover after reduced exposure duration (3 days) showed higher growth rates after treatment with s-metolachlor than with isoproturon. Taxonomic identifications showed that species like Melosira varians, Nitzschia dissipata and Cocconeis placentula were not affected by the herbicide exposure. Other species like Eolimna minima and Navicula reichardtiana were more sensitive. Studying diatoms according to their trophic mode showed that facultative heterotroph specieswere statistically significantly favoured by isoproturon exposure at the highest concentration. Results obtained with s-metolachlor exposure showed a disturbance of cell multiplication rather than that of photosynthesis. These results suggest that photosynthesis inhibitors like isoproturon favour species able to survive when the autotroph mode is inhibited

Comportement thermo-hydro-mécanique des massifs rocheux fracturés

The purpose of this research is to model Thermo-Hydro-Mechanical behavior of fractured rock mass regarding a nuclear waste redepository. For this, a methodology of modeling was proposed and was applied to a real underground site (EDF site at Nouvelle Romanche). This methodology consists, in a first step, to determine hydraulic and mechanical REV. Beyond the greatest of these REV, development of a finite element code allows to model all the fractures in an explicit manner. The homogenized mechanical properties are determined in drained and undrained boundary conditions by simulating triaxial tests that represent rock mass subject to loading. These simulations allow to study the evolution of hydraulic and mechanical properties as a function of stress state. Drained and undrained boundary conditions enable to discuss the validity of assimilation of a fractured rock mass to a porous medium. The simulations lead to a better understanding of the behavior of the fractured rock masses and allow to show the dominant role of the shear behavior of the fractures on the hydraulic and mechanical homogenized properties. From a thermal point of view, as long as conduction is dominant, thermal properties of the rock mass are almost the same as those the intact rock.L'objet de cette recherche est de modéliser le comportement Thermo-Hydro-Mécanique des massifs rocheux fracturés en vue du stockage de déchets radioactifs. A cette fin, nous avons été amené à proposer une méthodologie de modélisation des massifs rocheux fracturés qui a été appliquée à un site souterrain réel (Site EDF de Nouvelle Romanche). Cette méthodologie consiste, dans un premier temps, à rechercher les VER hydraulique et mécanique. Au dessus du plus grand de ces VER, les développements effectués dans un programme d'éléments finis permettent de modéliser toutes les fractures de manière explicite. On détermine les propriétés mécaniques homogénéisées en condition drainée et non drainée en simulant des essais triaxiaux représentatifs du massif soumis à un chargement. Ces simulations permettent d'analyser l'évolution des propriétés hydrauliques homogénéisées avec l'état de contraintes. La réalisation des expériences de type drainé et non drainé permet de discuter de la pertinence de l'assimilation d'un milieu fracturé à un milieu poreux. Ces simulations ont mis en évidence, en particulier, le rôle du comportement en cisaillement des fractures sur les propriétés homogénéisées mécaniques et hydrauliques. Du point de vue de la thermique, tant que le mode principal de propagation de la chaleur est la conduction, les propriétés thermiques homogénéisées sont peu différentes des propriétés thermiques de la matrice rocheuse

Learning the Language of Biological Sequences

International audienceLearning the language of biological sequences is an appealing challenge for the grammatical inference research field.While some first successes have already been recorded, such as the inference of profile hidden Markov models or stochastic context-free grammars which are now part of the classical bioinformatics toolbox, it is still a source of open and nice inspirational problems for grammatical inference, enabling us to confront our ideas to real fundamental applications. As an introduction to this field, we survey here the main ideas and concepts behind the approaches developed in pattern/motif discovery and grammatical inference to characterize successfully the biological sequences with their specificities

Vision-based interface for grasping intention detection and grip selection : towards intuitive upper-limb assistive devices

Assistive devices for indivuals with upper-limb movement often lack controllability and intuitiveness, in particular for grasping function. In this work, we introduce a novel user interface for grasping movement control in which the user delegates the grasping task decisions to the device, only moving their (potentially prosthetic) hand toward the targeted object

Searching for Smallest Grammars on Large Sequences and Application to DNA

International audienceMotivated by the inference of the structure of genomic sequences, we address here the smallest grammar problem. In previous work, we introduced a new perspective on this problem, splitting the task into two different optimization problems: choosing which words will be considered constituents of the final grammar and finding a minimal parsing with these constituents. Here we focus on making these ideas applicable on large sequences. First, we improve the complexity of existing algorithms by using the concept of maximal repeats when choosing which substrings will be the constituents of the grammar. Then, we improve the size of the grammars by cautiously adding a minimal parsing optimization step. Together, these approaches enable us to propose new practical algorithms that return smaller grammars (up to 10\%) in approximately the same amount of time than their competitors on a classical set of genomic sequences and on whole genomes of model organisms

Pondération d'automates obtenus par alignements partiels de séquences protéiques

National audienceL'identification de la fonction d'une protéine à partir de sa séquence d'acides aminés est un enjeu majeur en bioinformatique. Pour répondre à ce défi, l'équipe Dyliss a proposé un modèle statistique pour caractériser des familles fonctionnelles de protéines nommé protomate, un automate pondéré construit à partir d'un multiple alignement partiel et local d'un échantillon d'apprentissage de séquences : chaque colonne de chaque alignement partiel et local est associée à un état dans le protomate. Actuellement, le poids d'un état est calculé en prenant en compte seulement la colonne dont il est issu, mais du fait de la partialité de l'alignement, cette colonne ne contient pas toutes les séquences de l'échantillon d'apprentissage. Nous proposons ici une modification du calcul de ces poids qui prend en compte les séquences protéiques de l'échantillon qui ne passent pas dans la colonne. De plus, un protomate calcule pour une séquence un score d'appartenance à la famille qu'il modélise qui repose sur la comparaison de la probabilité que la séquence appartienne à la famille selon le protomate avec la probabilité d'appartenance selon un modèle aléatoire. Cependant la distribution de ce modèle n'était pas calculée de manière homogène au calcul de l'appartenance selon le protomate, nous avons donc proposé une modification de ce modèle de sorte à rendre les deux calculs plus cohérents

Learning local substitutable context-free languages from positive examples in polynomial time and data by reduction

International audienceTo study more formally the approach by reduction initiated by ReGLiS, we propose a formal characterization of the grammars in reduced normal form (RNF) which can be learned by this approach. A modification of the core of ReGLiS is then proposed to ensure returning RNF grammars in polynomial time. This enables us to show that local substitutable languages represented by RNF context-free grammars are identifiable in polynomial time and thick data (IPTtD) from positive examples